Effects Of MrgC Receptors On Morphine-induced Activation Of Glial Cells In The Spinal Cord And Their Mechanism

Mrg (Mas-related gene receptors, Mrg, also known as sensory neuron-specific receptor) mRNA are expressed uniquely in small-sized neuron in trigeminal ganglia (TG) and dorsal root ganglion (DRG). Intrathecal administration of the MrgC receptor agonist bovine adrenal medullary8-22(BAM8-22) has been demonstrated to inhibit the development of morphine tolerance. Glial cells are widely distributed in the central nervous system and play an important role in the pathogenesis of chronic pain. Studies have shown that glial cells are involved in the development and maintenance of morphine tolerance.The present study was conducted using behavioral, immunohstochemical techniques to examine:(1) the role of MrgC receptors in morphine tolerance (2) the effects of MrgC receptors on morphine-induced activation of glial cells. Results showed that intermittent administration of BAM8-22on days1,3,5inhibited me development of morphine tolerance. Chronic treatment with morphine activated spinal microglia and astrocytes, manifested by an increase in the expression of OX-42and GFAP, respectively and,hypertrophy and protuberant as well.Intermittent co-administration of BAM8-22inhibited these alterations and also the upregulation of P2X4receptors in microglia.This study indicates that intermittently activation of MrgC receptors can inhibit the morphine-incuced activation of microglia and astrocytes was ascribed to the inhibition of morphine tolerance.